Many synthetic polymeric membranes are made from hydrophobic polymers because they have desirable bulk properties such as flexibility, thermal stability, and chemical stability. However, the surfaces of such membranes are not suitable for applications requiring interactions with aqueous solutions, low protein adsorption, controlled ion exchange capacity, and controlled surface chemical reactivity.
It is often desirable to provide a porous membrane with a hydrophilic surface, which nevertheless retains the bulk properties of the underlying hydrophobic membrane. Such membranes are important in filtration applications that require the passage of aqueous fluids through the membranes. Additionally, porous hydrophilic membranes have important biological applications (e.g., as implantable medical devices), and use in assays relying on the capture and/or immobilization of biomolecules (e.g., nucleic acids or proteins) on a membrane surface. Therefore, the process of coating a hydrophobic surface should not diminish flow through efficiency of the membrane. Thus, processes that minimize pore clogging are essential for generating useful membranes comprising hydrophilic surfaces.
To render hydrophobic membranes hydrophilic, a wetting agent, such as a surface-active agent, can be added to a polymeric system being used to cast the membrane. Typically such coatings are only temporary, and the membrane so coated cannot be subjected to repeated wetting and drying procedures without loss of wettability. Further, exposure to any process fluid can generally extract the coating. This is particularly undesirable when processing biological fluids or contacting cells whose continued viability is desired.
Additional methods of casting membranes rely on the inclusion of hydrophilic cross-linkable monomers in a casting solution of dissolved hydrophobic polymer. Upon casting, a semi-crystalline polymer with hydrophilic surface properties is formed. See, e.g., U.S. Pat. Nos. 5,079,272 and 5,158,721.
Another method of preparing hydrophilic membranes involves graft polymerizing a hydrophilic monomer onto the surface of a porous hydrophobic polymeric membrane substrate. A typical example of a photochemical grafting process used to modify a hydrophobic surface with hydrophilic polymers is described in U.S. Pat. No. 5,468,390.
A number of patents also describe the covalent immobilization of hydrophilic polymers to a hydrophobic substrate using a photoreactive molecule covalently bound to the polymer, i.e., through a linking molecule. See, e.g., U.S. Pat. Nos. 4,973,493; 4,979,959; 5,002,582; 5,217,492; 5,258,041; 5,263,992; 5,414,075; 5,512,329; 5,563,056; 5,637,460; and 5,714,360.
U.S. Pat. No. 4,917,793 discloses directly coating a cross-linked polymer having desired surface properties on porous polytetrafluoroethylene membrane. The polytetrafluoroethylene membrane is exposed to a reagent bath comprising a free radical polymerizable monomer, a polymerization initiator and cross-linking agent (e.g., such as a difunctional molecule) in a solvent comprising water and a water miscible, polar, organic solvent under conditions to effect free radical polymerization of the monomer and coating of the porous membrane with the cross-linked polymer. The use of chemical crosslinking reagents that are typically tetrafunctional, results in highly branched three-dimensional structures that reduce the membrane's flow-through efficiency by plugging pores. Generally, rapid pore blockage is associated with the formation of an interpenetrating network of cross-linked hydrophilic difunctional molecules in high concentrations (see, e.g., as shown in FIG. 1A).
Such a method of modifying hydrophobic surfaces with hydrophilic molecules generally has the disadvantage of trapping excessive polymer on the membrane. This phenomenon can rapidly plug membrane pores irreversibly, leading to a rapid decline in flow rate and an increase in pressure required to filter molecules through the membrane. Further, membranes produced have high levels of extactables and demand longer rinsing cycles. Additionally, processes for making such membranes may require significant amounts of coating monomer or polymer (e.g., 6-12%) and a long incubation time to achieve a uniformly coated surface.